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Vaccination with mRNA-encoded nanoparticles drives early maturation of HIV bnAb precursors in humans.

Publication ,  Journal Article
Willis, JR; Prabhakaran, M; Muthui, M; Naidoo, A; Sincomb, T; Wu, W; Cottrell, CA; Landais, E; deCamp, AC; Keshavarzi, NR; Kalyuzhniy, O ...
Published in: Science
July 31, 2025
Published version (DOI) Link to item

A leading HIV vaccine strategy requires a priming immunogen to induce broadly neutralizing antibody (bnAb) precursors, followed by a series of heterologous boosters to elicit somatic hypermutation (SHM) and produce bnAbs. In two randomized, open-label phase 1 human clinical trials, IAVI G002 in the United States and IAVI G003 in Rwanda and South Africa (IAVI, International Aids Vaccine Initiative), we evaluated the safety and immunogenicity of mRNA-encoded nanoparticles as priming immunogens (both trials) and first-boosting immunogens (IAVI G002). The vaccines were generally safe and well tolerated, except that 18% of IAVI G002 participants experienced skin reactions. Priming induced bnAb precursors with substantial frequencies and SHM; heterologous boosting elicited increased SHM, affinity, and neutralization activity toward bnAb development; and elicited antibodies exhibited precise bnAb structural mimicry. The results establish clinical proof of concept that heterologous boosting can advance bnAb precursor maturation and demonstrate bnAb priming in Africa, where the HIV burden is highest.

Duke Scholars

Georgia Doris Tomaras
Author Georgia Doris Tomaras Surgery, Surgical Sciences
David Charles Montefiori
Author David Charles Montefiori Surgery, Surgical Sciences

Published In

Science

DOI

10.1126/science.adr8382

EISSN

1095-9203

Publication Date

July 31, 2025

Volume

389

Issue

6759

Start / End Page

eadr8382

Location

United States

Related Subject Headings

  • mRNA Vaccines
  • Young Adult
  • Vaccination
  • South Africa
  • Somatic Hypermutation, Immunoglobulin
  • Rwanda
  • Nanovaccines
  • Male
  • Immunogenicity, Vaccine
  • Immunization, Secondary
 

Citation

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MLA
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Willis, J. R., Prabhakaran, M., Muthui, M., Naidoo, A., Sincomb, T., Wu, W., … Schief, W. R. (2025). Vaccination with mRNA-encoded nanoparticles drives early maturation of HIV bnAb precursors in humans. Science, 389(6759), eadr8382. https://doi.org/10.1126/science.adr8382
Willis, Jordan R., Madhu Prabhakaran, Michelle Muthui, Ansuya Naidoo, Troy Sincomb, Weiwei Wu, Christopher A. Cottrell, et al. “Vaccination with mRNA-encoded nanoparticles drives early maturation of HIV bnAb precursors in humans.” Science 389, no. 6759 (July 31, 2025): eadr8382. https://doi.org/10.1126/science.adr8382.
Willis JR, Prabhakaran M, Muthui M, Naidoo A, Sincomb T, Wu W, et al. Vaccination with mRNA-encoded nanoparticles drives early maturation of HIV bnAb precursors in humans. Science. 2025 Jul 31;389(6759):eadr8382.
Willis, Jordan R., et al. “Vaccination with mRNA-encoded nanoparticles drives early maturation of HIV bnAb precursors in humans.” Science, vol. 389, no. 6759, July 2025, p. eadr8382. Pubmed, doi:10.1126/science.adr8382.
Willis JR, Prabhakaran M, Muthui M, Naidoo A, Sincomb T, Wu W, Cottrell CA, Landais E, deCamp AC, Keshavarzi NR, Kalyuzhniy O, Lee JH, Murungi LM, Ogonda WA, Yates NL, Corcoran MM, Phulera S, Musando J, Tsai A, Lemire G, Sein Y, Muteti M, Alamuri P, Bohl JA, Holman D, Himansu S, Leav B, Reuter C, Lin L-A, Ding B, He C, Straus WL, MacPhee KJ, Regadas I, Nyabundi DV, Chirchir R, Anzala O, Kimotho JN, Kibet C, Greene K, Gao H, Beatman E, Benson K, Laddy D, Brown DM, Bronson R, Jean-Baptiste J, Gajjala S, Rikhtegaran-Tehrani Z, Benner A, Ramaswami M, Lu D, Alavi N, Amirzehni S, Kubitz M, Tingle R, Georgeson E, Phelps N, Adachi Y, Liguori A, Flynn C, McKenney K, Zhou X, Owuor DC, Owuor SA, Kim S-Y, Duff M, Kim JY, Gibson G, Baboo S, Diedrich J, Schiffner T, Shields M, Matsoso M, Santos J, Syvertsen K, Kennedy A, Schroeter M, Vekemans J, Yates JR, Paulson JC, Hyrien O, McDermott AB, Maenetje P, Nyombayire J, Karita E, Ingabire R, Edward V, Muturi-Kioi V, Maenza J, Shapiro AE, McElrath MJ, Edupuganti S, Taylor BS, Diemert D, Ozorowski G, Koup RA, Montefiori D, Ward AB, Karlsson Hedestam GB, Tomaras G, Hunt DJ, Muema D, Sok D, Laufer DS, Andrews SF, Nduati EW, Schief WR. Vaccination with mRNA-encoded nanoparticles drives early maturation of HIV bnAb precursors in humans. Science. 2025 Jul 31;389(6759):eadr8382.
Journal cover image

Published In

Science

DOI

10.1126/science.adr8382

EISSN

1095-9203

Publication Date

July 31, 2025

Volume

389

Issue

6759

Start / End Page

eadr8382

Location

United States

Related Subject Headings

  • mRNA Vaccines
  • Young Adult
  • Vaccination
  • South Africa
  • Somatic Hypermutation, Immunoglobulin
  • Rwanda
  • Nanovaccines
  • Male
  • Immunogenicity, Vaccine
  • Immunization, Secondary